Jun Shimokawa, Tatsuya Toma, Tohru Fukuyama

Review Author

Anonymous

(15)

Review

23 February 2017

Reproducible, but Yields Lower Than Described

Overall Rating

Reproducibility

Impact

Clarity

Versatility

Details

Summary:

An efficient method for the synthesis of diazoacetates from the coresponding bromoacetates and N,N'-ditosylhydrazine has been described. In fact, diazoacetates can be prepared from various alcohols by acylation with bromoacetyl bromide, followed by a treatment with N,N'-ditosylhydrazine without isolation of bromoacetate intermediates. Ease of operation with the stable crystalline reagent as well as a short reaction time offer a useful alternative to the conventional methods.

The Reaction of Interest:

I was using the described protocol for the synthesis of several diazocompounds. Thus, cyclohexyl diazoacetate (55-72% yield), cyclopentyl diazoacetate (60%), benzyl diazoacetate (74%), phenyl diazoacetate (58%), and diazoacetophenone (63%) were prepared via this method.

Practical Observations:

- The reaction is well-reproducible, although, yields are slightly lower then described (i.e. 58% vs 74% for phenyl diazoacetate and 74% vs 90% for benzyl diazoacetate).

- According to the protocol, 2 equiv of N,N'-ditosylhydrazine and 5 equiv of DBU are required for the reaction, which produces a lot of TsOH by-product.

- The reaction is scalable up to 30 mmol.

Recommendations:

- Lower reagents loading can be used. Thus, the use of 1.5 equiv of N,N'-ditosylhydrazine and 3 equiv. did not decrease the yield of products. The amount of solvents also can be reduced.

- The use of inert atmosphere is generally gives slightly better yield of products.

- A significant amount of TsOH precipitate is formed upon quenching of the reaction mixture, which troubles further extraction of product. The precipitate can be removed by filtration before exctraction of a diazocompound.